High E2

[Jin23]

I have never read anything about the gut detoxing estrogen. Where did you read this? Testosterone is made in the body or injected into it and never enters the gut. Once estrogen is in the blood stream how would the gut do that? The liver breaks it down and removes it from the blood stream.

All circulating sex hormones have their part to play in the gut bro. They actually meaningfully modulate your microbiome.

Google Učenjak

scholar.google.com

However, how much does the gut microbiota effect the level of your peripheral blood hormone levels is a nother thing entirely.

 

[buck]

All circulating sex hormones have their part to play in the gut bro. They actually meaningfully modulate your microbiome.

Google Učenjak

scholar.google.com

However, how much does the gut microbiota effect the level of your peripheral blood hormone levels is a nother thing entirely.

Please explain how the gut itself detoxifies the E2 as that was what is being discussed in the previous post.
Everything in the body affects everything is the body.
So yes if the diet i put in my gut has a negative impact on the liver then it can effect hormone levels and that is a no brainer to me.
I don't worry about the butterfly effect to much.
But if the thing in question has no noticeable impact itself then the point is moot to me. Others can do as they please.

 

[readalot]

Maybe your shbg droped and you have more free T and thus more E2

Funny you mention I am doing a follow up experiment to answer this one more time. Last time I did it I only estimated FT with Vermeulen and FT was invariant to SHBG drop (via oxandrolone) under the constraints of constant exogenous Test dosing.

This time I am measuring TT (LCMS) and FT (equilibrium dialysis) with 200 mg/week Test Cyp (trough at E3.5D) with and without 50 mg/day oxandrolone.

For many years now we have been been talking about this at ExcelMale and TNation. The hypothesis is that lowering SHBG may increase percent FT but does not increase absolute FT (sponge theory of SHBG).

All the greatest hits in one thread.

SHBG and Free Testosterone - Everything You Need to Know

Table of Contents Testosterone Fractions in Men How SHBG Influences Free Testosterone What Factors Influence Your SHBG Levels? How Do You Know if Your SHBG Levels Are High? How to Lower SHBG and Automatically Increase Free Testosterone Levels? Raise Your Total Testosterone Level Lower Your...

www.excelmale.com

Nice summary:

SHBG and Free Testosterone - Everything You Need to Know

Table of Contents Testosterone Fractions in Men How SHBG Influences Free Testosterone What Factors Influence Your SHBG Levels? How Do You Know if Your SHBG Levels Are High? How to Lower SHBG and Automatically Increase Free Testosterone Levels? Raise Your Total Testosterone Level Lower Your...

www.excelmale.com

The formulas are not producing false results. The confusion arises because they are given in the form

FT = f(TT, SHBG, ALB)

This makes sense when you want to estimate free testosterone and the three function parameters are relatively easy to measure. However, this form creates the perception that total testosterone drives free testosterone, and also encourages the misperception that total testosterone can be treated as constant and directly under our control in the case of TRT. Instead, consider rearranging the formula to

TT = f1(FT, SHBG, ALB)

I've been arguing that this form is more natural with respect to physiology. Free testosterone is driven proportionally by the production rate of testosterone, or by the testosterone dose rate in those on TRT. The relative constancy of free testosterone allows for your observation above that "[Free testosterone] controls TTotal, so that TTotal increases or decreases porporcionalmente at the level of SHBG." If you invert the Vermeulen calculation and ignore albumin then the equation looks something like this:

TT = (a + b * FT + SHBG) * FT / (c * FT + d)

This does imply that total testosterone increases monotonically with SHBG when free testosterone is fixed.

 

[Jin23]

Funny you mention I am doing a follow up experiment to answer this one more time. Last time I did it I only estimated FT with Vermeulen and FT was invariant to SHBG drop (via oxandrolone) under the constraints of constant exogenous Test dosing.

This time I am measuring TT (LCMS) and FT (equilibrium dialysis) with 200 mg/week Test Cyp (trough at E3.5D) with and without 50 mg/day oxandrolone.

For many years now we have been been talking about this at ExcelMale and TNation. The hypothesis is that lowering SHBG may increase percent FT but does not increase absolute FT (sponge theory of SHBG).

All the greatest hits in one thread.

SHBG and Free Testosterone - Everything You Need to Know

Table of Contents Testosterone Fractions in Men How SHBG Influences Free Testosterone What Factors Influence Your SHBG Levels? How Do You Know if Your SHBG Levels Are High? How to Lower SHBG and Automatically Increase Free Testosterone Levels? Raise Your Total Testosterone Level Lower Your...

www.excelmale.com

Nice summary:

SHBG and Free Testosterone - Everything You Need to Know

Table of Contents Testosterone Fractions in Men How SHBG Influences Free Testosterone What Factors Influence Your SHBG Levels? How Do You Know if Your SHBG Levels Are High? How to Lower SHBG and Automatically Increase Free Testosterone Levels? Raise Your Total Testosterone Level Lower Your...

www.excelmale.com

Should be interesting to see your results. How much do you see the potential variance of results by equilibrium d. as a potential hindrance to your endeavors?

SHBG is an interesting topic indeed. It's much more complicated that was once thought, especially it's interaction with estrogen (have you read this?
https://www.cell.com/iscience/fullt...m/retrieve/pii/S2589004221003825?showall=true ) and the androgen-shbg complex, or more specifically when an androgen binds to the shbg-shbgR complex (some tissues cAMP is increased, some tissues increased, also the type of steroid also maters).

Post cycling, my shbg has fluctuated anywhere from 110 to 70. Fluid balance is a pita for me, as is sleep (fragmented sleep). Anything, and I do mean anything that has a negative effect on estrogenic signaling I notice immediately - with further exasperation of sleep quality taking the most noticeable hit. ELISA says my E2 is around 20 pgml, which is not surprising with such a high shbg, but I'm assuming the high SHBG is significantly lowering the free E2 fraction. From personal experience, shbg's effects on estrogen are far from negligible and we should expand on it more often, rather then focusing only on free androgens ...

Btw, I have to say I very much dislike math and if we get too technical, I'll start loosing track.

 

[readalot]

Should be interesting to see your results. How much do you see the potential variance of results by equilibrium d. as a potential hindrance to your endeavors?

That is the weak spot for my experiment. I have run labs head to head (see Parts I and II here) but never run reps on the same sample at a given lab. Hence I have no idea the method precision at a lab for ED.

So to summarize, on the same blood sample roughly approximating peak blood levels 24 hours after injection for TC (of course off on the TP part):

TT (Quest MS) = 1103 ng/dl
TT (Labcorp Esoterix LCMS) = 1081 ng/dl
TT (Labcorp Burlington (LCMS) = 993 ng/dl
FT (Quest ED) = 24.5 ng/dl
FT (Labcorp Esoterix ED) = 22.7 ng/dl
FT (adj direct FT EIA) = 19.3 ng/dl
cFTV (Vermeulen) ~ 27.1 ng/dl
adjusted cFTV (90% of CFTV) ~ 24.4 ng/dl
TruT ~ 38.9 ng/dl
A few of takeaways for me:
Both Labcorp and Quest agree pretty well on measured FT via ED even through reference ranges are quite different as we discussed before).
The adjusted direct FT still gets you in the ballpark although the low price of the FT by ED using @Nelson Vergel's Discounted Labs make it stupid easy to get FT by ED with very low cost.
Interlab variability with the two Labcorp HoST sites was ~8% for my blood sample.
TruT calculator as it currently exists on the website SUCKS unless Labcorp and Quest are both measuring FT wrong. Neither Quest nor Labcorp line up with the training set TruT claims matches their calculated values. If Labcorp and Quest are both full of sh*t then why are we telling guys to keep ordering these tests LOL?

RIP TruT (CFTZ) v1.0:

 

[readalot]

SHBG is an interesting topic indeed. It's much more complicated that was once thought, especially it's interaction with estrogen (have you read this?
https://www.cell.com/iscience/fullt...m/retrieve/pii/S2589004221003825?showall=true ) and the androgen-shbg complex, or more specifically when an androgen binds to the shbg-shbgR complex (some tissues cAMP is increased, some tissues increased, also the type of steroid also maters).

Post cycling, my shbg has fluctuated anywhere from 110 to 70. Fluid balance is a pita for me, as is sleep (fragmented sleep). Anything, and I do mean anything that has a negative effect on estrogenic signaling I notice immediately - with further exasperation of sleep quality taking the most noticeable hit. ELISA says my E2 is around 20 pgml, which is not surprising with such a high shbg, but I'm assuming the high SHBG is significantly lowering the free E2 fraction. From personal experience, shbg's effects on estrogen are far from negligible and we should expand on it more often, rather then focusing only on free androgens ...

I remember reading or scanning when it when first published. Great points on E2/fE2/SHBG. That is the next piece to "get right" after we clean up this TT/FT/SHBG debacle. If the above hypothesis is proven correct and absolute fT is invariant to SHBG under constant exogenous Testosterone then that raises the same question for fE2 and E2. FT aromatization yields fE2, which then quickly equilibrates with E2 via SHBG. Hence my hypothesis is that fE2 would be shown to have same relationship with SHBG as fT, no?

Looking forward to the day we can get agreement on how to measure fT and fE2 for that matter (CDC Host program, etc.).

Side note: although Tru T claims to get all the non linear allosteric binding isotherms right, it's accuracy against current fT ED measurements is horrible. Vermeulen still kicking its ass all these years later.

There seems to still be much uncertainty around harmonized FT measurement.

 

[Jin23]

If the above hypothesis is proven correct and absolute fT is invariant to SHBG under constant exogenous Testosterone then that raises the same question for fE2 and E2. FT aromatization yields fE2, which then quickly equilibrates with E2 via SHBG. Hence my hypothesis is that fE2 would be shown to have same relationship with SHBG as fT, no?

I don't think I'm really following. Why the adjective "absolute" in front of fT? What would be non absolute fT?

Regarding the idea that fT is unchanging on TRT regardless of SHBG levels (that is what you're saying right?), besides inverting some math equations, what other evidence steers you in that direction?

If E2 allosterically binds to shbg then obviously not. The level of shbg and e2 would both effect fE2 numbers. However if you're trying to superimpose the same logic from your fT hypothesis then I suppose yes, but then again, I'm not quite sure what exactly would give you the authority to do that? These are different molecules and besides that, looking at biological processes as a single monolithically equation that produces the same general outcome in all circumstances would be a fraudulent endeavour. This is biology, not maths after all and you need to look at outcomes not at single mechanisms of action.

Regarding your thoughts on trut and other calcs, lab measurements ... My outlook on the whole fT topic is that none of these tools is accurate. So just pick one and gauge your subjective results/well being to their numbers. But I'd have to underline the same thing again; judging androgenicety or anabolism just on the basis of fT levels would again be wrong as there is a myriad of factors that effect this process which aren't only reliant on free androgens, albeit that might be the most relevant factor. We know how shbg complex effects cAMP, for instance, prostate cancer cell cAMP is stimulated by e2 with the presence of shbg and not without (I'm suggesting that SHBG and its receptor might have roles in cellular signaling pathways, potentially influencing androgen action in a more complex manner then we might have thought before) and supposedly, androgens also diffuse from shbg in small capillaries and this wouldn't be reflected in peripheral venus blood samples. What if shbg negatively effects androgen ar binding, and how does it effect androgens non genomic actions and how relevant are those to your subjective experience on androgens androgenic effects? Just some examples to illustrate my point ...

 

[readalot]

1. I don't think I'm really following. Why the adjective "absolute" in front of fT? What would be non absolute fT?

2. Regarding the idea that fT is unchanging on TRT regardless of SHBG levels (that is what you're saying right?), besides inverting some math equations, what other evidence steers you in that direction?

3. If E2 allosterically binds to shbg then obviously not. The level of shbg and e2 would both effect fE2 numbers. However if you're trying to superimpose the same logic from your fT hypothesis then I suppose yes, but then again, I'm not quite sure what exactly would give you the authority to do that? These are different molecules and besides that, looking at biological processes as a single monolithically equation that produces the same general outcome in all circumstances would be a fraudulent endeavour. This is biology, not maths after all and you need to look at outcomes not at single mechanisms of action.

4. Regarding your thoughts on trut and other calcs, lab measurements ... My outlook on the whole fT topic is that none of these tools is accurate. So just pick one and gauge your subjective results/well being to their numbers. But I'd have to underline the same thing again; judging androgenicety or anabolism just on the basis of fT levels would again be wrong as there is a myriad of factors that effect this process which aren't only reliant on free androgens, albeit that might be the most relevant factor. We know how shbg complex effects cAMP, for instance, prostate cancer cell cAMP is stimulated by e2 with the presence of shbg and not without (I'm suggesting that SHBG and its receptor might have roles in cellular signaling pathways, potentially influencing androgen action in a more complex manner then we might have thought before) and supposedly, androgens also diffuse from shbg in small capillaries and this wouldn't be reflected in peripheral venus blood samples. What if shbg negatively effects androgen ar binding, and how does it effect androgens non genomic actions and how relevant are those to your subjective experience on androgens androgenic effects? Just some examples to illustrate my point ...

Numbered your paragraphs above for ease of reply and clarity.


1.Absolute in front of FT to call out serum FT level vs relative FT (%; FT/TT). Lowering SHBG for constant FT would increase relative FT (percentage FT) but not absolute FT or just FT. Repetition for effect.

2. Yes, FT invariant to SHBG under constraint of constant exogenous T source (limit as T is introduced continuously to remove PK peaks/troughs). I know you said you don't like math but the blow by blow has been covered in literature....

Chapter 12 - Hypothalamo-Pituitary Unit, Testis, and Male Accessory Organs

Read this chapter. Chapter 12 - Hypothalamo-Pituitary Unit, Testis, and Male Accessory Organs https://www.sciencedirect.com/science/article/pii/B9780323479127000123?via%3Dihub From https://www.sciencedirect.com/book/9780323479127/yen-and-jaffes-reproductive-endocrinology

www.excelmale.com

3. Regarding E2/fE2 perhaps my hand wave above is a stretch regardless of the FT situation. fE2 production would be paracrine process so my thought experiment is probably way too simplistic given SHBG's role (free hormone hypothesis still a matter of active research):

Test Dosage vs Levels for Cycle Recommendation

Let’s journal club this bad boy. Tissue dependent:

forums.t-nation.com

A Reappraisal of Testosterone’s Binding in Circulation: Physiological and Clinical Implications

This appraisal of the dynamics of testosterone binding to proteins and of the free hormone hypothesis offers guidance for the application of free testosterone i

academic.oup.com

I am an anonymous internet poster so I have no authority at all. I always just discuss matters based on the existing knowledge available. Definitely won't get an appeal to authority from me.

4. You raise good points here but I hunger to understand what FT is and how to measure it. I have compared FT measurements head to head with CFTV and Tru T for years (see excelmale for those interested). TruT researchers claimed their model was improvement over law of mass action models and shared alot of data on the binding relationships. Unfortunately it fails horribly against Vermeulen with actual FT-ED serum data.

I agree with you; my scope was to accurately measure FT. What that means for anabolic/androgenic effects is another matter entirely covered by your great points.

I'll settle to see how my revised experiment turns out. May add in a replicate by measuring again with same lab at trough the following week as well.

Really appreciate your thoughts on all this.

 

[Jin23]

I am an anonymous internet poster so I have no authority at all. I always just discuss matters based on the existing knowledge available. Definitely won't get an appeal to authority from me.

Eh, no, it's not what I meant, I wasnt being judgemental. That came out wrong, lost in translation, too underslept. Was just aquiring why would you think that the same principle could be translated to e2.

The rest of the reply was just me being critical towards the whole discussion because I was to low on energy and didn't see much point in discussion this topic in such depth ...

Ah, you keep linking towards some long winded topics on other forums ... I'm sry but I'm too tired, not going to go read that whole discussion. But you're basically saying that there is validity towards the claim of fT being locked while on exogenous androgens and it's more then just some math equation permutation? Can you post a quick summation?

 

[readalot]

Can you post a quick summation?

Sorry for late response. Will post my latest experiment in a few weeks. I've provided summary and exhaustive links to the concept.

 

[readalot]

quick summation

Here and a couple posts up...

Help Understanding Bloodwork

Good afternoon Meso. I got bloodwork done recently and there are some concerns I have with it, as well as some things that I don't quite understand (if I should be worried, etc). For reference, I am currently taking 12.5mg enclomiphene, 10mg ibutamoren ED as well as some other supplements that...

thinksteroids.com

Edit:

Help Understanding Bloodwork

Good afternoon Meso. I got bloodwork done recently and there are some concerns I have with it, as well as some things that I don't quite understand (if I should be worried, etc). For reference, I am currently taking 12.5mg enclomiphene, 10mg ibutamoren ED as well as some other supplements that...

thinksteroids.com